The problem of cocaine dependence remains a major medical, social, and legal concern, and there is a pressing need for a broadly effective treatment approach. Dozens of medications have been evaluated in clinical trials and, despite these efforts, not one has gained FDA approval as a treatment for cocaine dependence. Behavioral interventions, such as cognitive behavioral therapy, have been moderately effective, indicating that non-pharmacological treatment approaches warrant additional consideration. Recent data suggest that moderate physical exercise attenuates cravings for cigarettes and improves cognitive functioning in humans. These data coincide with several reports in rodents showing that exercise (i.e., wheel running) reduced cocaine self-administration, though the effects of exercise on cocaine use in humans has not been investigated. Of interest, exercise has been shown to be reinforcing in humans, and this may account for its potential efficacy as an addiction treatment. We propose a placebo-controlled, between-subjects design to evaluate the effects of exercise on improved fitness, cocaine use, and craving for cocaine. Given existing data showing beneficial effects of exercise on cigarette smoking, we will also monitor changes in smoking and craving for nicotine as a positive control. The Specific Aims include: 1) To evaluate the effects of exercise (running vs. walking 30 min per session, 3 times per week, over 4 consecutive weeks) versus placebo (sitting for the same period of time and duration) on basic fitness measures;2) To evaluate the effects of exercise on objective and subjective measures of cocaine and nicotine use and craving. All participants will be adults who meet DSM criteria for current cocaine- and nicotine-dependence, who are seeking treatment for their cocaine addiction. Computerized cognitive behavioral therapy (CBT) will be the standard treatment provided to all participants. A platform of contingency management will also be used to encourage attendance (not abstinence). Exercise sessions will be performed on a NordicTrack Elite 9500 PRO Treadmill, and a physician or nurse practitioner will be present during all physical activity sessions. This application represents an important research effort with considerable public health significance in that it will establish a program for evaluating the effects of exercise on craving and use of cocaine and nicotine in cocaine-dependent individuals. PUBLIC HEALTH RELEVANCE: This application describes a placebo-controlled, between-subjects study to evaluate the effects of exercise on improved fitness, cocaine use, and craving for cocaine in cocaine-dependent individuals.